• BMB Reports
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• 제42권9호
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• pp.561-567
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• 2009

Although many plant-derived phenolic compounds display antioxidant effects in biological systems, their mechanism of action remains controversial. In this study, the mechanism by which p-coumaric acid (p-CA) performs its antioxidant action was investigated in bovine aortic endothelial cells under oxidative stress due to high levels of glucose (HG) and arachidonic acid (AA), a free fatty acid. p-CA prevented lipid peroxidation and cell death due to HG+AA without affecting the production of reactive oxygen species. The antioxidant effect of p-CA was not decreased by buthionine-(S,R)-sulfoximine, an inhibitor of cellular GSH synthesis. In contrast, pretreatment with p-CA caused the induction of peroxidases that decomposed t-butyl hydroperoxide in a p-CA-dependent manner. Furthermore, the antioxidant effect of p-CA was significantly mitigated by methimazole, which was shown to inhibit the catalytic activity of 'p-CA peroxidases' in vitro. Therefore, it is suggested that the induction of these previously unidentified 'p-CA peroxidases' is responsible for the antioxidant effect of p-CA.

• The Korean Journal of Nuclear Medicine
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• 제22권1호
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• pp.21-26
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• 1988

Serum TBII measured by radioreceptor assay using $^{125}I-bovine$ TSH and porcine thyroid well membrane was checked before, 6 months and 12 months after initiation of thionamide regimens in 63 Graves' disease patients and was related with their remission state. 1) A significant difference (p < 0.01) in pre-treatment TBII was noted between the remitted [N = 45, TBII $40.9{\pm}18.2%$ $(mean{\pm}S.D)$] and the unremitted (N = 18, TBII $64.1{\pm}15.3%$) groups. 2) After 6 months of therapy, TBII were significantly decreased in both groups (to $20.2{\pm}10.3%$ and to $45.2{\pm}16.3%$, p<0.05 for each group) 3) At 12th month, TBII activities were not significantly decreased compared to the 6th month levels in both groups. 4) 3 of the 58 patients who were initially TBII positive (over 15%) converted negative. All the 3 belonged to the remitted group. 5) No significant differences were seen in initial and posttreatment TBII levels between propylthiouracil treated (N = 36) and methimazole treated (N = 27) cases. with above mentioned results, we observed that the TBII decreased significantly with 6 months of thionamide therapy and concluded that the pretreatment measurement of serum TBII may be clinically useful in predicting the response to thionamide regimen in the treatment of Graves' disease.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.547-553
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• 2004

The pyrrolizidine alkaloids (PAs), contained in a number of traditional remedies in Africa and Asia, show wide variations in metabolism between animal species but little work has been done to investigate differences between animal strains. The metabolism of the PA senecionine (SN) in Fischer 344 (F344) rats has been studied in order to compare to that found in the previously investigated Sprague-Dawley (SO) rats (Drug Metab. Dispos. 17: 387, 1989). There was no difference in the formation of ($\pm$) 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, bioactivation) by hepatic microsomes from either sex of SO and F344 rats. However, hepatic microsomes from male and female F344 rats had greater activity in the Noxidation (detoxication) of SN by 88% and 180%, respectively, when compared to that of male and female SD rats. Experiments conducted at various pH showed an optimum pH of 8.5, the optimal pH for flavin-containing monooxygenase (FMO), for SN N-oxidation by hepatic microsomes from F344 females. In F344 males, however, a bimodal pattern was obtained with activity peaks at pH 7.6 and 8.5 reflecting the possible involvement of both cytochrome P450 (CYP) and FMO. Use of specific inhibitors (SKF525A, 1-benzylimidazole and methimazole) showed that the N-oxide of SN was primarily produced by FMO in both sexes of F344 rats. In contrast, SN N-oxide formation is known to be catalyzed mainly by CYP2C11 rather than FMO in SD rats. This study, therefore, demonstrated that there were substantial differences in the formation of SN N-oxide by hepatic microsomes from F344 and SD rats and that this detoxification is catalyzed primarily by two different enzymes in the two rat strains. These findings suggest that significant variations in PA biotransformation can exist between different animal strains.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제13권2호
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• pp.120-125
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• 2013

Purpose: McCune-Albright syndrome (MAS) is caused by activating mutations in the GNAS gene, resulting in peripheral precocious puberty, caf$\acute{e}$-au-lait spots, and polyostotic fibrous dysplasia (POFD). The aim of the present study was to describe the diverse clinical and endocrine characteristics of patients with MAS. Methods: Seven patients with MAS were included in this study and medical charts were reviewed retrospectively for following parameters: patient's sex and age at diagnosis, POFD, ovarian cysts, and precocious puberty. Results: The mean age at diagnosis was $5.8{\pm}4.2$ years. One patient was male (14%) and the other six patients were female (86%). Peripheral precocious puberty was associated with 6 patients (86%). Five patients manifested premature menarche as early as 2 to 5 years of age. Letrozole was administered to 4 patients, tamoxifen to one patient and GnRH agonist to one patient. Five females developed ovarian cysts. Thyroid function tests were performed in all patients and one patient showed hyperthyroidism (14%) and has been treated with methimazole. One patient presented with pseudohypoparathyroisdism, phosphaturia, calciuria suggesting hypophosphatemic rickets. Six patients (86%) revealed POFD. One patient had symptoms of optic nerve compression and secondary esotropia and 2 patients had bone pain. Conclusion: This study described clinical characteristics and endocrine complications of patients with MAS. Careful physical examinations with history taking and serial endocrine function tests should be needed to detect complications such as endocrinologic hyperfunction and POFD.

• Sleep Medicine and Psychophysiology
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• 제18권1호
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• pp.40-44
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• 2011

Narcolepsy is a sleep disorder, which is characterized by excessive daytime sleepiness (EDS) that is typically associated with cataplexy, sleep fragmentation and other REM sleep-related phenomenon such as sleep paralysis and hypnagogic hallucination. Narcoleptic symptoms can be developed from various medical or neurological disorders. A 17-year-old male patient admitted for the evaluation of EDS which started three-month ago. He slept more than 18 hours a day with cataplexy and hypnagogic hallucination. He was obese with body mass index (BMI) of 30.4 kg/$m^2$. After admission he was newly diagnosed to the thyrotoxicosis. T3 391.2 ng/dL (60-181), free T4 4.38 ng/dL (0.89-1.76), TSH <0.01 ${\mu}IU$/mL (0.35-5.5) were measured. His pulse rate ranged 70-90 beats per minute and blood pressure ranged 150/100-120/70 mmHg. Polysomnography revealed many fragmentations in sleep with many positional changes (81 times/h). Sleep onset latency was 33.5 min, sleep efficiency was 47.9%, and REM latency from sleep onset was delayed to 153.6 min. REM sleep percent was increased to 27.1%. Periodic limb movement index was 13.4/h. In the multiple sleep latency test (MSLT), average sleep latency was 0.4 min and there were noted 3 SOREMPs (Sleep Onset REM sleep period) on 5 trials. We couldn't discriminate the obvious sleep-wake pattern in the actigraph and his HLA DQB1 $^*0602$ type was negative. His thyroid function improved following treatment with methimazole and propranolol. Vital sign maintained within normal range. Cataplexy was controlled with venlafaxine 75 mg. Subjective night sleep continuity and PLMS were improved with clonazepam 0.5 mg, but the EDS were partially improved with modafinil 200-400 mg. Thyrotoxicosis might give confounding role when we were evaluating the EDS, though sleep fragmentation was one of the major symptoms of narcolepsy, but enormous amount of it made us think of the influence of thyroid hormone. The loss of sleep-wake cycle, limited improvement of EDS to the stimulant treatmen, and the cataplexy not supported by HLA DQB1 $^*0602$ should be answered further. We still should rule out idiopathic hypersomnia and measuring CSF hypocretin level would be helpful.

• The Korean Journal of Nuclear Medicine
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• 제14권2호
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• pp.53-60
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• 1980

The radioimmunoassay of TSH (human thyrotropin) was performed by utilizing anti-h-TSH antibody and purified human thyrotropin supplied from Daiichi Radioisotope company in Japan. From Jan. 1978 through Aug. 1980 the serum concentration of TSH was measured on 41 cases with various thyroid diseases, and 22 normal persons. Among 41 cases, 9(22%) were primary hypothyroidism, 17(41%) Graves' disease, 8(20%), subacute or chronic lymphocytic thyroiditis, and 7(17%) nodular goiter. The results were as follows: 1) The normal values of serum TSH in 22 cases of control group were $4.2{\pm}1.7{\mu}U/ml(1.9-7.4{\mu}U/ml)$, which were within normal range in kit used in this study. 2) The serum TSH concentration in 9 cases with primary hypothroidism were $97.1{\pm}116.4{\mu}U/ml(14.0-300{\mu}U/ml)$, which were significantly elevated as compared with normal control values. 3) The serum TSH concentration in 17 cases with Graves' disease were $1.5{\pm}0.6{\mu}U/ml(1.0-2.5{\mu}U/ml)$, which were below than normal control. 4) The serum TSH concentration in 8 cases with subacute or chronic lymphocytic thyroiditis. revealed wide ranges ($1.6-220{\mu}U/ml$) according to the state of thyroid function. 5) The serum TSH values in 7 cases with nodular goiters were $2.3{\pm}2.0{\mu}U/ml$, which were strictly within normal levels. 6) The serum TSH levels were elevated during prolonged treatment with Tapazole (Methimazole) without serial check of the serum TSH concentration in Graves' disease, so the serial measurement of serum TSH concentration was considered of available index of thyroid states.

• Asian-Australasian Journal of Animal Sciences
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• 제21권6호
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• pp.794-800
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• 2008

In the present study, two trials were conducted to evaluate the effects of hyper- and hypothyroid status on the redox balance of broiler chickens. In Trial 1, 3 groups of broiler chickens were randomly subjected to one of the three treatments: subcutaneous administration of triiodothyronine (T3, $150{\mu}g/kg$ BW), methimazole (MMI, 150 mg/kg BW), or saline. The blood, liver and heart were sampled at 3 h after injection. In Trial 2, three groups of 20 broiler chickens were randomly fed with one of the three diets: control, dietary supplementation of T3 (1.5 mg/kg diet) or MMI (1 g/kg diet) for 7 days. In trial 1, the plasma concentrations of T3 and T3 to thyronine ratio (T3/T4) were significantly increased by T3 injection. Plasma levels of thiobarbituric acid reacting substances (TBARS) tended to be increased (p = 0.067) by both T3 and MMI treatments while the ferric reduced/antioxidant capacity (FRAP) was increased only by MMI treatment. Acute T3 treatment had no significant effect on the activities of superoxide dismutase (SOD) and the concentrations of FRAP and TBARS in either liver or heart tissue. In contrast, the hepatic activities of SOD were decreased (p<0.05) while the cardiac levels of FRAP were significantly increased (p<0.0001) by MMI treatment. In chronic treatments, the rectal temperature of chickens was significantly decreased (p<0.05) by MMI treatment. The circulating T3 levels were significantly increased (p<0.05) by long-term T3 treatment, and showed a trend to decrease in MMI treatment. The plasma concentrations of TBARS were significantly (p<0.05) increased by MMI treatment. All the redox parameters measured in either liver or heart were not significantly altered by either long-term T3 or MMI treatment except that the hepatic SOD activities were significantly augmented by T3 treatment. The result showed that neither acute nor long-term elevation of circulating T3 levels induced lipid peroxidation in broiler chickens. The enhanced enzymatic antioxidant system (SOD in cardiac tissue) may be involved in the protection of the bird to increased oxidative challenge. The responses of redox balance to changed thyroid state seem to be tissue specific.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.585-591
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• 2010

Purpose : Graves' disease is the most common cause of hyperthyroidism in children and adolescents. In this study, we investigated the natural course and the prognostic factors of Graves' disease in Korean children and adolescents. Methods : One-hundred thirteen (88 girls and 25 boys) patients were included in this study. A retrospective analysis was made of all patients who were diagnosed with Graves' disease. The following parameters were recorded and analyzed: patient's sex, age at diagnosis, duration of disease, laboratory findings, symptoms and signs, and family history of autoimmune thyroid disease. Results : All patients were initially treated with antithyroid drugs, either methimazole (93.8%) or propylthiouracil (6.2%). Antithyroid drugs had been discontinued in 75 (66.4%) of 113 patients. Of these 75 patients, 23 (20.4%) relapsed after $25.5{\pm}33.7$ months. Thirteen (11.5%) of 23 patients, who experienced the first relapse, showed a second remission. However, 2 (1.8%) of 13 patients relapsed again. Euthyroid state could not be achieved by antithyroid drugs in 1 patient, and radioactive iodine therapy was performed. The older the patient at diagnosis, the greater the likelihood of remission ($P$=0.034). Conclusion : Age at diagnosis seems to be a prognostic factor in Korean children and adolescents with Graves' disease, and should be taken into account in treatment plan determination.